Variaciones de las células de cuadrícula y de posicionamiento de la corteza entorrinal y del giro dentado de 6 humanos de 56 a 87 años / Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years

Introducción: La relación entre la corteza entorrinal y el hipocampo ha sido estudiada por diferentes autores, que han destacado la importancia de las células de cuadrícula, las células de posicionamiento y la conexión trisináptica en los procesos que regulan: la persistencia de la memoria espacial, explícita y reciente, y su posible afección con el envejecimiento. Objetivo: Observar si existen diferencias en el tamaño y número de células de cuadrícula contenidas en la lámina iii de la corteza entorrinal y en la capa granular del giro dentado del hipocampo de pacientes mayores. Métodos: Realizamos estudios posmortem del cerebro de 6 sujetos de edades comprendidas entre los 56 y 87 años. Los cortes de cerebros que contenían el giro dentado del hipocampo y la corteza entorrinal adyacente se tiñeron con el método de Klüver-Barrera, después se midió, mediante el programa Image J, el área neuronal individual, el área neuronal total, así como el número de neuronas, contenidas en cuadrículas rectangulares a nivel de la lámina iii de la corteza entorrinal y la lámina ii del giro dentado y se llevó a cabo un análisis estadístico. Resultados: Se ha observado una reducción de la población celular de la capa piramidal externa de la corteza entorrinal, así como de las neuronas de la capa granular del giro dentado relacionada con el envejecimiento. Conclusión: Nuestros resultados indican que el envejecimiento produce una disminución en el tamaño y la densidad neuronal en las células de cuadrícula de la corteza entorrinal y de posicionamiento del giro dentado.(AU)

Introduction: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. Objective: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. Methods: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. Results: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. Conclusion: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.(AU)

Glucose metabolism, hippocampal subfields and cognition in first-episode and never-treated schizophrenia

Background: Previous studies have indicated that glucose metabolism and altered hippocampal structure and function play a pivotal role in cognitive deficits in schizophrenia (SZ). This study was designed to explore the inter-relationship between glucose metabolism, hippocampal subfield volume, and cognitive function in the antipsychotics-naive first episode (ANFE) SZ patients. Methods: We chose the fasting insulin, glucose, and insulin resistance (HOMA-IR) index as biomarkers of glucose metabolism. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). The hippocampal subfield volume, glucose metabolism biomarkers, and cognitive function were evaluated in 43 ANFE SZ and 29 healthy controls (HCs). Results: Compared with HCs, SZ patients had higher fasting blood glucose and insulin levels and HOMA-IR (all p < 0.05). Correlation analysis revealed that category fluency performance was positively associated with fasting glucose level. Fasting insulin or HOMA-IR was positively associated with the hippocampal subfield volume in patients (all p<0.05). Moreover, the spatial span index score was associated with the volume of the right presubiculum, subiculum, and right hippocampal tail. In addition, multiple regression analysis found that the interaction effects of insulin × right fimbria or insulin × left fimbria were independent predictors of the MCCB total score. Conclusions: Our findings suggest that abnormal glucose metabolism and cognitive decline occur in the early stage of SZ. The interaction between abnormal glucose metabolism and hippocampal subfields was associated with cognitive functions in SZ. (AU)

Resveratrol ameliorates the behavioural and molecular changes in rats exposed to uninephrectomy: role of hippocampal SIRT1, BDNF and AChE

Subtle memory and cognitive changes may occur in uninephrectomized (Unix) patients long before the development of chronic kidney disease, such changes may be unnoticed. The dietary polyphenol, Resveratrol, displayed various neuroprotective effects, its role in chronic kidney disease is an area of intense studies. This work was designed to investigate the behavioural and molecular changes that may occur following 7 months of Unix in rats, and to determine whether Resveratrol intake can improve such pathology. Male Wistar rats were divided into three groups: sham operated, Unix and Unix group treated with Resveratrol (20 mg/kg/day). Rats were subjected to series of behavioural testing, different biochemical parameters along with RT-PCR and immunohistochemistry of the hippocampal tissue to track the development of functional or structural brain changes. Anxiety behaviour and reduced spatial memory performance were observed in rats 7 months post-nephrectomy; these deficits were remarkably reversed with Resveratrol. Among the species typical behaviour, burrowing was assessed; it showed significant impairment post-nephrectomy. Resveratrol intake was almost able to increase the burrowing behaviour. Decreased SIRT1 in immune-stained sections, oxidative stress, inflammatory changes, and increased AChE activity in hippocampal homogenates were found in Unix rats, and Resveratrol once more was capable to reverse such pathological changes. This work has investigated the occurrence of behavioural and structural brain changes 7 months following Unix and underlined the importance of Resveratrol to counterbalance the behavioural impairment, biochemical and brain pathological changes after uninephrectomy. These findings may raise the possible protective effects of Resveratrol intake in decreased kidney function. (AU)

Machine learning-based automated planning for hippocampal avoidance prophylactic cranial irradiation

Purpose Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer. Materials and methods Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets. Results A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases. Conclusion The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques (AU)

Amnesia global transitoria: una entidad infrecuente pero presente en Pediatría / Transient global amnesia: an infrequent entity but present in Pediatrics

Introducción: La amnesia global transitoria es una entidad caracterizada por la aparición súbita de amnesia anterógrada con amnesia retrógrada variable, conservando intacta la memoria inmediata. No asocia otros déficits neurológicos. La recuperación es progresiva en pocas horas, habitualmente menos de 12, aunque suele persistir amnesia del episodio y presentar posteriormente cefalea leve. Caso clínico. Niño de 10 años, sin antecedentes de interés, que consulta en Urgencias por aparición brusca de amnesia retrógrada de las últimas 48 horas, así como incapacidad para la fijación de nueva información. Se mostraba ansioso y desorientado, y repetía la misma pregunta varias veces. La exploración neurológica por lo demás era estrictamente normal y negaba cefalea u otra sintomatología asociada. No antecedente de traumatismo craneoencefálico. Se realiza analítica sanguínea y gasometría venosa, sin alteraciones significativas; tóxicos en orina, negativos; TAC cerebral que descarta patología intracraneal aguda y punción lumbar, que es normal. Ingresa en planta de hospitalización con evolución favorable, con cese espontáneo de la clínica a las 8 horas, permaneciendo amnesia del episodio, con resto de la memoria conservada. Comentarios. La fisiopatología de la amnesia global transitoria no está del todo aclarada, aunque hay trabajos que sugieren un origen vascular de la misma, produciéndose durante estos episodios una hipoperfusión del lóbulo temporal medial. Es una entidad típica de adultos de mediana edad y ancianos siendo excepcional en pediatría. Sin embargo, debemos considerar este diagnóstico ante niños con clínica típica, normalidad de la neuroimagen y resolución espontánea de los síntomas.(AU)

Introduction: Transient global amnesia is an entity characterized by the sudden onset of anterograde amnesia with variable retrograde amnesia, preserving immediate memory intact. It is not associated with other neurological deficits. Recovery is progressive in a few hours, usually less than 12 hours, although amnesia of the episode usually persists and later presents mild headache. Case report. A 10-year-old boy, with no previous history of interest, consulted the emergency department for sudden onset of retrograde amnesia of the last 48 hours, as well as inability to fix new information. He was anxious and disoriented and repeated the same question several times. The neurological examination was otherwise strictly normal, and he denied headache or other associated symptoms. There was no history of cranioencephalic trauma. Blood analysis and venous blood gas analysis were performed, with no significant alterations; urine toxins were negative; brain CAT scan ruled out acute intracranial pathology and lumbar puncture was normal. She was admitted to the hospital ward with favorable evolution, with spontaneous cessation of the clinical symptoms after 8 hours, remaining amnesia of the episode, with the rest of the memory preserved. Comments. The pathophysiology of transient global amnesia has not been fully clarified, although some studies suggest a vascular origin, with hypoperfusion of the medial temporal lobe occurring during these episodes. It is a typical entity of middle-aged and elderly adults, being exceptional in pediatrics. However, we should consider this diagnosis in children with typical clinical symptoms, normal neuroimaging and spontaneous resolution of symptoms.(AU)

Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer / Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease

Introducción: En el mundo, alrededor de 50 millones de personas padecen demencia; la forma más común es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo diseñar estudios que permitan ampliar el conocimiento sobre su aparición y desarrollo, para proponer diagnósticos tempranos y/o posibles tratamientos. Una de las estrategias metodológicas que se han desarrollado son los modelos transgénicos murinos para el estudio de los factores involucrados en su etiología, y entre ellos, el estrés oxidativo y la respuesta inmune.DesarrolloSe realizó una búsqueda de artículos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revisión abordamos dos factores que han sido estudiados de forma independiente: el estrés oxidativo y la respuesta inmune en modelos transgénicos para la EA, y se discute la relación que existe entre ellos y que impacta en la pérdida de la plasticidad sináptica y estructural, produciendo como efecto final el deterioro cognitivo.ConclusiónEsta revisión describe posibles mecanismos en donde participan el estrés oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relación entre estos elementos que conducen hacia el deterioro cognitivo. (AU)

Introduction: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response.DevelopmentWe searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment.ConclusionThis review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment. (AU)

La plasticidad sináptica mediada por endocannabinoides y trastornos por consumo de drogas / Endocannabinoid-mediated synaptic plasticity and substance use disorders

Las drogas impactan en los circuitos de recompensa cerebrales y originan dependencia y adicción, lo que se define actualmente como trastornos por consumo de drogas. Los mecanismos de plasticidad sináptica en dichos circuitos son cruciales en el desarrollo de la conducta adictiva, y los endocannabinoides, entre los que destacan la anandamida y el 2-araquidonil-glicerol, participan en la normal neuroplasticidad. Se sabe que los trastornos por consumo de drogas se asocian, entre otros fenómenos, a disrupción de la plasticidad sináptica mediada por endocannabinoides. Estas moléculas median neuroplasticidad de corta duración y perdurable. Respecto a la de corta duración, destacan fenómenos de carácter «inhibidor», como la supresión de la inhibición inducida por despolarización y la supresión de la excitación inducida por despolarización; y otros «desinhibidores», como la desinhibición de la actividad neuronal, sobre todo en el núcleo estriado, y la supresión de la liberación GABA en el hipocampo. Por otra parte, las drogas pueden alterar la normal potenciación perdurable y la depresión perdurable mediadas por endocannabinoides. Los endocannabinoides también influyen en el desarrollo de hipofrontalismo y sensibilización causados por las drogas. En fin, el abuso de drogas origina una disrupción en la plasticidad sináptica de circuitos cerebrales involucrados en la adicción y en ello juega un destacado papel la alteración de la normal actividad endocannabinoide. Ello facilita los cambios anómalos cerebrales y el desarrollo de conductas adictivas que caracterizan a los trastornos por consumo de drogas. (AU)

Drugs impact brain reward circuits, causing dependence and addiction, in a condition currently described as substance use disorders. Mechanisms of synaptic plasticity in these circuits are crucial in the development of addictive behaviour, and endocannabinoids, particularly anandamide and 2-arachidonyl-glycerol, participate in normal neuroplasticity. Substance use disorders are known to be associated with disruption of endocannabinoid-mediated synaptic plasticity, among other phenomena. Endocannabinoids mediate neuroplasticity in the short and the long term. In the short term, we may stress «inhibitory» phenomena, such as depolarisation-induced suppression of inhibition and depolarisation-induced suppression of excitation, and such «disinhibitory» phenomena as long-lasting disinhibition of neuronal activity, particularly in the striatum, and suppression of hippocampal GABA release. Drugs of abuse can also disrupt normal endocannabinoid-mediated long-term potentiation and long-term depression. Endocannabinoids are also involved in the development of drug-induced hypofrontality and sensitisation. In summary, substance abuse causes a disruption in the synaptic plasticity of the brain circuits involved in addiction, with the alteration of normal endocannabinoid activity playing a prominent role. This facilitates abnormal changes in the brain and the development of the addictive behaviours that characterise substance use disorders. (AU)

Swimming exercise versus L-carnosine supplementation for Alzheimer’s dementia in rats: implication of circulating and hippocampal FNDC5/irisin

Recent studies have suggested that irisin may act as a potential neurokine. Exercise and L-carnosine supplementation showed neuroprotective effects in Alzheimer’s disease (AD)–like conditions. However, the regulation of irisin in the hippocampus of streptozotocin (STZ)–induced memory impairment and its relation to insulin signalling remain to be investigated. This study was designed to compare the effect of swimming exercise and L-carnosine intake on serum, CSF and hippocampal irisin in rats received intracerebroventricular (ICV) injection of STZ. Rats were recruited in swimming paradigm, received oral carnosine (100 mg/kg/day) or vehicle treated. After 5 weeks, rats were sacrificed after neurobehavioural testing. CSF and serum irisin were determined. Hippocampal tissues were used to assess expression of FNDC5/irisin, BDNF and proteins related to insulin signalling, in addition to β-amyloid peptide and phosphorylated tau protein levels. We observed decreased hippocampal, but not CSF or serum, irisin in ICV-STZ-injected rats. Exercise and carnosine intake almost normalized hippocampal FNDC5/irisin expression which was associated with reduced soluble β-amyloid peptide and phosphorylated tau protein, improved BDNF and insulin signalling proteins, with corresponding mitigated cognitive impairments. However, hippocampal FNDC5/irisin was not correlated with serum or CSF irisin levels. Histologically, both interventions ameliorated the hippocampal damage in STZ-injected rats. The current study reveals that carnosine is equivalent to exercise in reversing cognitive decline and Alzheimer’s biomarkers. In both interventions, enhancement of hippocampal FNDC5/irisin and insulin signalling may be involved in mediating these neuroprotective effects. (AU)

Efecto de la exposición a bajas dosis de ozono en la expresión de la interleucina 17A durante el proceso de neurodegeneración progresiva en el hipocampo de ratas / Effect of exposure to low doses of ozone on interleukin 17A expression during progressive neurodegeneration in the rat hippocampus

Introducción: La exposición crónica a bajas dosis de ozono causa un estado de estrés oxidativo y pérdida de la regulación de la respuesta inflamatoria, lo cual lleva a un proceso de neurodegeneración progresiva.ObjetivoEstudiar el efecto de la exposición crónica a bajas dosis de ozono sobre la concentración de IL-17A y su expresión en neuronas, microglía, astrocitos y células T en hipocampo de ratas.MétodosSe utilizaron 72 ratas Wistar, divididas en 6 grupos (n = 12): control (sin ozono) y expuestos a ozono (0,25 ppm, 4 h diarias) durante 7, 15, 30, 60 y 90 días, respectivamente. Seis sujetos de cada grupo fueron procesados para cuantificar IL-17A por ELISA y los 6 restantes para inmunohistoquímica (frente a IL-17A y GFAP, Iba1, NeuN o CD3).ResultadosLos datos obtenidos por el ELISA mostraron un incremento significativo en las concentraciones de IL-17A en los grupos de 7, 15, 30 y 60 días de exposición, comparados con el control (p < 0,05). Los resultados muestran que las neuronas del hipocampo son las células con una mayor inmunorreactividad frente a IL-17A entre los 60 y 90 días de exposición a ozono; además, se observó un aumento de astrocitos activados en los grupos de 30 y 60 días de exposición.ConclusiónLa exposición a ozono induce un incremento en la expresión de la IL-17A, principalmente en las neuronas hipocampales, acompañado de una activación de astrocitos en el hipocampo de ratas durante el proceso de neurodegeneración progresiva, similar a lo que ocurre en la enfermedad de Alzheimer en humanos. (AU)

Introduction: Chronic exposure to low doses of ozone causes oxidative stress and loss of regulation of the inflammatory response, leading to progressive neurodegeneration.ObjectiveWe studied the effect of chronic exposure to low doses of ozone on IL-17A concentration and expression in neurons, microglia, astrocytes, and T cells in the rat hippocampus.MethodsWe used 72 Wistar rats, divided into 6 groups (n = 12): a control group (no ozone exposure) and 5 groups exposed to ozone (0.25 ppm, 4 h daily) for 7, 15, 30, 60, and 90 days. We processed 6 rats from each group to quantify IL-17A by ELISA; the remaining 6 were processed for immunohistochemistry (against IL-17A and GFAP, Iba1, NeuN, and CD3).ResultsThe ELISA study data showed a significant increase in IL-17A concentrations in the 7-, 15-, 30-, and 60-day exposure groups, with regard to the control group (P < .05). Furthermore, they indicate that hippocampal neurons were the cells showing greatest immunoreactivity against IL-17A between 60 and 90 days of exposure to ozone; we also observed an increase in activated astrocytes in the 30- and 60-day exposure groups.ConclusionExposure to ozone in rats induces an increase in IL-17A expression, mainly in hippocampal neurons, accompanied by hippocampal astrocyte activation during chronic neurodegeneration, similar to that observed in Alzheimer disease in humans. (AU)

The impact of external stress factors on hippocampus volume during antidepressant treatment

Background and objectives: Magnetic resonance imaging (MRI) studies suggest that depression is associated with volumetric hippocampal changes. Investigations of these structures during antidepressant therapy is therefore important, however, volumetric studies are rare in this case. We aimed to study the effect of AD treatment on volumetric changes in hippocampus depending on stress factors in depressive patients.MethodsThirty patients with major depressive disorder (MDD) underwent MRI of the brain on the day of admission and at the time of stabilization of acute depressive symptomatology by venlafaxine. The presence of long-lasting stress factors in these patients was investigated by the social readjustment rating scale questionnaire.ResultsNo significant differences were found in hippocampi volumes before and after venlafaxine treatment. However, regression analysis revealed significant positive relation between stress factors and volumetric hippocampus change during AD treatment.ConclusionIt seems that antidepressant treatment by venlafaxine could be more suitable in the MDD patients with presence of stress-factors. (AU)

Memory state and hippocampal histomorphology in Wistar rat following monosodium glutamate-induced neurotoxicity; role of aqueous extract of Aloe Barbadensis

This study assessed the effect of varying doses of aqueous extract of Aloe barbadensis on the cellular changes of hippocampal cells, oxidative and memory state of Wistar rats following monosodium glutamate-induced neurotoxicity. Eighty Wistar rats (8 weeks) were randomly as-signed into 4 groups of 20 rats; Group 1 received 3 mL/kg of distilled water. Groups 2, 3 and 4 received 3 g/kg/day of MSG. In addition, groups 3 and 4 received 100 and 200 mg/kg/day of AB ex-tract respectively. Administration was done orally for 28 days in all groups. Five rats per group were sacrificed weekly over a 4-week period. Memory was assessed using radial arm maze on the last day of administration. Following brain harvest, one cerebral hemisphere was homogenized for oxidative state assessment, while the other was fixed in 10% neutral buffered formalin and stained with H&E for hippocampal histomorphology. Data obtained were analyzed using student t-test and p value < 0.05 was considered significant. Across the 4-week period, group 2 rats showed significant increase in time spent to identify baited arms, significant reduction in density of apparentlynormal neurons and oligodendrocyte in CA 1-3 regions of hippocampus, and significant increase in reduced glutathione when compared with other groups. However, no significant differences were noted between groups 1, 3 and 4 for the above stated parameters. The study concluded that MSG caused hippocampal neuronal and oligodendrocytes degeneration and impairment of memory. These anomalies are prevented by 100 and 200 mg/kg of Aloe barbadensis

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The effect of regulatory aerobic exercise on lipoproteins index of plasma in epileptic male rat

There is no report on the evaluation aerobic exercise on lipoproteins and Atherogenic Index of Plasma (AIP) in epileptic male rats. In the present study our purpose was to elucidate the effect of regulatory aerobic exercise on Lipoproteins and (AIP) in epileptic male rat by pentylentetrazol. In this experimental study, 40 male rats randomly divided into 2 main different epileptic (kindling) and non-epileptic groups (n = 20). The epileptic groups were kindled by intraperitoneal injection of 40 mg/kg pentylentetrazol (PTZ), then divided into two epileptic subgroups, including the aerobic exercise and without exercise. The non-epileptic groups were divided into two subgroups including aerobic exercise and without exercise. After 6-week exercise rats were deep anesthetized by ketamine, and then blood was taken. Data were analyzed by t-test and ANOVA. The epileptic male rats that received aerobic exercise increased significantly the seizure of parameters S2L and S4L, compared with the epileptic group that did not receive regular exercise P < 0.05. Also, in the aerobic exercise groups decreased the parameters S5D and SD compared with the control group P < 0.001. The exercise significantly de-creased total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDLP) as compared with the epileptic group without exercise P < 0.001. The present study indicates that the aerobic regularly exercise not only decreased the duration of seizures, but also reduce the vascular risk factor in epileptic group rats

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La respuesta sistémica Th17/IL-17A aparece antes del proceso neurodegenerativo en el hipocampo de ratas expuestas a bajas dosis de ozono / Systemic Th17/IL-17A response appears prior to hippocampal neurodegeneration in rats exposed to low doses of ozone

Introducción: La exposición a dosis bajas de O3 conduce a un estado de estrés oxidativo. Algunos estudios muestran que el estado de estrés oxidativo puede modular tanto el SNC como la inflamación sistémica, que son importantes para el desarrollo de la enfermedad de Alzheimer. Objetivo: Evaluar la frecuencia de células tipo Th17, la concentración de IL-17A en plasma y la inmunorreactividad del hipocampo a IL-17A en ratas expuestas a dosis bajas de O3.Métodos: Ciento ocho ratas Wistar machos fueron divididas en 6 grupos (n = 18) con los siguientes tratamientos: control (sin O3) y O3 (0,25 ppm, diario por 4h) durante 7, 15, 30, 60 y 90 días. De cada grupo se decapitaron 12 animales, se tomó una muestra de sangre periférica para aislar el plasma y las células mononucleares. La IL-17A plasmática se evaluó mediante LUMINEX y la frecuencia de células de tipo Th17 por citometría de flujo. Las ratas restantes se anestesiaron y se perfundieron para inmunohistoquímica en el hipocampo. Resultados: Muestran que la exposición durante 7 días a O3 produce un aumento significativo en la frecuencia de células tipo Th17 y los niveles de IL-17A en sangre periférica. Sin embargo, existe una disminución de Th17/IL-17A en la periferia desde el día 15. También se encontró un aumento de IL-17A en el hipocampo desde los 30 días de exposición. Conclusión: El O3 produce un efecto sistémico a corto plazo de tipo Th17/IL-17A y un aumento de IL-17A en el tejido del hipocampo durante el proceso neurodegenerativo crónico

Introduction: Exposure to low doses of O3 leads to a state of oxidative stress. Some studies show that oxidative stress can modulate both the CNS and systemic inflammation, which are important factors in the development of Alzheimer disease (AD).Objective: This study aims to evaluate changes in the frequency of Th17-like cells (CD3+CD4+IL-17A+), the concentration of IL-17A in peripheral blood, and hippocampal immunoreactivity to IL-17A in rats exposed to low doses of O3. Methods: One hundred eight male Wistar rats were randomly assigned to 6 groups (n = 18) receiving the following treatments: control (O3 free) or O3 exposure (0.25 ppm, 4hours daily) over 7, 15, 30, 60, and 90 days. Twelve animals from each group were decapitated and a peripheral blood sample was taken to isolate plasma and mononuclear cells. Plasma IL-17A was quantified using LUMINEX, while Th17-like cells were counted using flow cytometry. The remaining 6 rats were deeply anaesthetised and underwent transcardial perfusion for immunohistological study of the hippocampus. Results: Results show that exposure to O3 over 7 days resulted in a significant increase in the frequency of Th17-like cells and levels of IL-17A in peripheral blood. However, levels of Th17/IL-17A in peripheral blood were lower at day 15 of exposure. We also observed increased IL-17A in the hippocampus beginning at 30 days of exposure. Conclusion: These results indicate that O3 induces a short-term, systemic Th17-like/IL-17A effect and an increase of IL-17A in the hippocampal tissue during the chronic neurodegenerative process

Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats

In recent years, the beneficial impact of targeted gut microbiota manipulation in various neurological disorders has become more evident. Therefore, probiotics have been considered as a promising approach to modulate brain gene expression and neuronal pathways even in some neurodegenerative diseases. The purpose of this study was to determine the effect of probiotic biotherapy with combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the expression levels of proteins critical to neuronal apoptosis in hippocampus of lipopolysaccharide (LPS)-exposed rats. Four groups of animals (Control, LPS, Probiotic + LPS, and Probiotic) were treated with maltodextrin (placebo) or probiotic (109 CFU/ml/rat) for 2 weeks by gavage. On the 15th day, a single intraperitoneal dose of saline or LPS (1 mg/kg) was injected and 4 h later, protein assessment was performed by western blotting in hippocampal tissues. LPS significantly increased the Bax, Bax/Bcl-2 ratio, and cleaved caspase-3 expression along with decreased the Bcl-2 and procaspase-3 protein levels. However, probiotic pretreatment (L. helveticus R0052 + B. longum R0175) significantly downregulated the Bax and Bax/Bcl-2 ratio accompanied with upregulated Bcl-2 expression. Prophylactic treatment with these bacteria also attenuated LPS-induced caspase-3 activation by remarkably increasing the expression of procaspase-3 while reducing the level of cleaved caspase-3 in target tissues. Our data indicate that probiotic formulation (L. helveticus R0052 + B. longum R0175) alleviated hippocampal apoptosis induced by LPS in rats via the gut-brain axis and suggest that this probiotic could play a beneficial role in some neurodegenerative conditions

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Distinctive expression pattern of Peg10 in the mouse brain

Peg10 (paternally expressed 10) is a retrotransposon-derived gene that is highly conserved across mammalian species. Peg10 is involved in cell proliferation and differentiation, and is essential for placenta formation in mice. Although a number of studies have examined Peg10 expression in the placenta, its cellular localization in the brain is still unclear. The function of Peg10 in the brain is also unknown. Here, we examined Peg10 distribution in the mouse brain. In situ hybridization revealed intense expression of the gene in the core region of the accumbens nucleus, lateral division of the bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, premammillary nucleus, central amygdaloid nucleus and lateral parabrachial nucleus. Moderate to intense expression of Peg10 was also observed in monoaminergic nuclei such as the substantia nigra, dorsal raphe nucleus and locus coeruleus. These results suggest that Peg10 may play a role in motivational processes, emotional regulation, and autonomic functions in the brain. The findings also suggest that Peg10 may have contributed to the evolution of mammals, not only by participating in placenta formation, but also by regulating parental behavior and hormonal secretions necessary for maternal responsiveness

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Atomoxetine enhances memory and proliferation in adult male rat hippocampus

Atomoxetine (ATX) is a noradrenaline reuptake inhibitor used to treat Attention deficit hyperactive syndrome (ADHD), or improve cognition in normal subjects. The cognitive effects of ATX require inputs from the hippocampus. Moreover, proliferation is said to be located in the dentate gyrus (DG) of the hippocampus.In the present study, we hypothesised that ATX improves memory and proliferation of the adult rat hippocampus. To test this hypothesis, 5 intraperitoneal injections of ATX (30 mg/kg/day) over 5 consecutive days were delivered to rats. 30 minutes after the last injection, spatial memory was tested using the Novel location recognition (NLR) test. Proliferation of hippocampal cells was quantified using immunohistochemistry for the proliferative marker Ki67. ATX-treated rats showed cognitive enhancement in the NLR task and increase in cell proliferation in the Subgranular zone (SGZ) of the DG, compared to saline-treated controls. The results demonstrate that ATX is able to enhance cognition through increasing the levels of proliferation in the adult rat brains

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Neurotoxicidad cognitiva inducida por la radioterapia cerebral en adultos / Radiation-induced cognitive toxicity in adults

La toxicidad cognitiva inducida por la radioterapia craneal es una de las limitaciones mas importantes del tratamiento radioterapico y con mas impacto sobre la calidad de vida de los largos supervivientes de tumores cerebrales. Esta revision incluye una actualizacion del diagnostico clinico y radiologico de la toxicidad radioinducida con la incorporación de baterias neuropsicologicas y tecnicas avanzadas en neuroimagen. Ambas herramientas han permitido en los últimos anos no solo una mejor definicion de la disfuncion cognitiva, sino tambien la identificacion de los cambios anatomicos y funcionales asociados. La fisiopatologia subyacente implica diferentes estirpes celulares y vias de senalizacion molecular, y el mecanismo es multifactorial. Aunque no existe actualmente una estrategia terapeutica que haya demostrado una clara eficacia, varios estudios, incluyendo los que proponen respetar el hipocampo o el uso de la memantina, han resultado prometedores. Profundizar en el estudio de la toxicidad cognitiva inducida por la radioterapia permitira definir mejor los pacientes que se benefician de la radioterapia, asi como estudiar nuevas dianas terapeuticas para mejorar la calidad de vida de los pacientes con dano cerebral radioinducido

Cognitive toxicity induced by cranial radiation is one of the most important limitations of radiation therapy and has a significant impact on brain tumor survivors’ quality of life. This review comprehends an up to date of recent studies including complete neuropsychological battery and/or advanced neuroimaging techniques. These studies identified critical anatomical and/or functional brain areas related to radiation-induced brain injury, thus improving clinical and radiological diagnosis. Pathophysiological mechanisms underlying cognitive toxicity are complex and involve different cell lines and molecules. Although there is no currently therapeutic strategy that has a demonstrated efficacy, several studies including sparing of hippocampus or the use of memantine are quite promising. A better knowledge of the characteristics of cognitive toxicity induced by cranial radiation, will help us to identify patients who will benefit from treatment and also to examine new therapeutic targets in order to improve patients’ quality of life

Changes in MAP-2 and GFAP immunoreactivity in pup hippocampus during prepubertal and pubertal periods caused by maternal subclinical hypothyroidism

An absence of the thyroid hormone during the critical period of brain development causes delayed maturation of glial cells and neurons and decreases the number of hippocampal cells. This study aims to examine the impact of maternal subclinical hypothyroidism (SCH) on pup hippocampus during the prepubertal and pubertal periods by means of assessing the histopathological changes in astrocytes and neurons.Twelve Wistar albino pregnant rats were divided into two groups, Group H and Group C. Group C was designated as the control group and nothing was added to their drinking water. SCH was induced in Group H by administering 6-propyl-2-thiouracil (PTU) at a final concentration of 0.01% in the drinking water of pregnant rats for 21 days. Male pups for each group were divided evenly and evaluated on either day 15 (prepubertal) or 60 (pubertal) (7 pups in each group). At the end of the experimental period, the rats were sacrificed for analysis of brain tissue. Immunoreactivity intensities of MAP-2 and GFAP were evaluated in hippocampus tissue. Thyroid function was determined using ELISA. The structure of hippocampus was evaluated by hematoxylin-eosin staining. Finally, the TUNEL method was utilized to show apoptosis of hippocampus tissue. The results were analyzed statistically.The findings show that maternal SCH causes disruption in hippocampal cytoskeleton and dendritic organization, especially during the pubertal period, as well as a decrease in MAP-2 expression. We observed structural deformation in astrocytes, reduced astrocyte survival and GFAP expression. Finally, we found that the number of neuronal apoptotic cells tended to increase in the pubertal period

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Esclerosis hipocampal: evaluación volumétrica de las subestructuras del hipocampo utilizando resonancia magnética / Hippocampal sclerosis: volumetric evaluation of the substructures of the hippocampus by magnetic resonance imaging

Objetivo: Evaluar las subestructuras hipocampales utilizando resonancia magnética en pacientes con esclerosis hipocampal (EH), comparando los resultados con el análisis morfológico y la volumetría global del hipocampo. Método: Se incluyeron 25 controles y 25 pacientes con EH, cuyo diagnóstico fue extraído del informe de la junta institucional de epilepsia. Se utilizó FreeSurfer para el procesamiento de los estudios y la obtención de los datos volumétricos. El volumen fue valorado de manera global y por subestructura: fimbria, subiculum, presubiculum, fisura hipocampal, CA1, CA2-CA3, CA4 y giro dentado (GD). Se consideró p <0,05 como estadísticamente significativo. Resultados: Se observó una disminución estadísticamente significativa en el hipocampo homolateral al foco epileptógeno en 19 de los 25 casos (76,0%). A excepción de la fisura hipocampal, se observó una disminución en todas las subestructuras hipocampales homolaterales en la EH derecha (CA1, p = 0,0223; CA2-CA3, p = 0,0066; CA4-GD, p = 0,0066; fimbria, p = 0,0046; presubiculum, p = 0,0087; subiculum, p = 0,0017) y la EH izquierda (CA1, p <0,0001; CA2-CA3, p <0,0001; CA4-GD, p <0,0001; fimbria, p = 0,0183; presubiculum, p <0,0001; subiculum, p <0,0001). En cuatro casos de EH izquierda, ninguna de las subestructuras presentó alteración estadísticamente significativa; sin embargo, se observó una tendencia de atrofia, principalmente en CA2-CA3 y CA4-GD. Conclusión: Los hallazgos sugieren la utilidad de la evaluación de las subestructuras hipocampales para mejorar el desempeño de la imagen en el diagnóstico de la EH

Objective: The pathological classification of hippocampal sclerosis is based on the loss of neurons in the substructures of the hippocampus. This study aimed to evaluate these substructures in patients with hippocampal sclerosis by magnetic resonance imaging and to compare the usefulness of this morphological analysis compared to that of volumetric analysis of the entire hippocampus. Material and methods: We included 25 controls and 25 patients with hippocampal sclerosis whose diagnosis was extracted from the institutional epilepsy board. We used FreeSurfer to process the studies and obtain the volumetric data. We evaluated overall volume and volume by substructure: fimbria, subiculum, presubiculum, hippocampal sulcus, CA1, CA2-CA3, CA4, and dentate gyrus (DG). We considered p < 0.05 statistically significant. Results: We observed statistically significant decreases in the volume of the hippocampus ipsilateral to the epileptogenic focus in 19 (76.0%) of the 25 cases. With the exception of the hippocampal sulcus, we observed a decrease in all ipsilateral hippocampal substructures in patients with right hippocampal sclerosis (CA1, p=0.0223; CA2-CA3, p=0.0066; CA4-GD, p=0.0066; fimbria, p=0.0046; presubiculum, p=0.0087; subiculum, p=0.0017) and in those with left hippocampal sclerosis (CA1, p<0.0001; CA2-CA3, p<0. 0001; CA4-GD, p<0. 0001; fimbria, p=0.0183; presubiculum, p<0. 0001; subiculum, p<0. 0001). In four patients with left hippocampal sclerosis, none of the substructures had statistically significant alterations, although a trend toward atrophy was observed, mainly in CA2-CA3 and CA4-GD. Conclusion: The findings suggest that it can be useful to assess the substructures of the hippocampus to improve the performance of diagnostic imaging in patients with hippocampal sclerosis